title: Preliminary evaluation of a model of stimulant use, oxidative damage and executive dysfunction.
abstract: BACKGROUND
  Illicit stimulant use increases oxidative stress and oxidative stress has been found to be associated with deficits in memory, attention and problem-solving.
  
  
  OBJECTIVE
  To test a model of the association among oxidative DNA damage, a severe form of oxidative stress, and stimulant use, executive function and stimulant-use outcomes.
  
  
  METHODS
  Six sites evaluating 12-step facilitation for stimulant abusers obtained peripheral blood samples from methamphetamine-dependent (n = 45) and cocaine-dependent (n = 120) participants. The blood samples were submitted to a comet assay to assess oxidative DNA damage. Executive Dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), which is a reliable and valid self-report assessment of executive dysfunction, disinhibition and apathy. Stimulant-use measures included self-reported stimulant use and stimulant urine drug screens (UDS).
  
  
  RESULTS
  While more recent cocaine use (<30 days abstinence) was associated with greater oxidative DNA damage (W = 2.4, p < 0.05, d = 0.36), the results did not support the hypothesized relationship between oxidative DNA damage, executive dysfunction and stimulant use outcomes for cocaine-dependent patients. Support for the model was found for methamphetamine-dependent patients, with oxidative DNA damage significantly greater in methamphetamine-dependent patients with executive dysfunction (W = 2.2, p < 0.05, d = 0.64) and with executive dysfunction being a significant mediator of oxidative DNA damage and stimulant use during active treatment (ab = 0.089, p < 0.05). As predicted, neither disinhibition nor apathy were significant mediators of oxidative damage and future stimulant use.
  
  
  CONCLUSIONS
  These findings provide preliminary support for a model in which oxidative damage resulting from methamphetamine use results in executive dysfunction, which in turn increases vulnerability to future stimulant use.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. winhusen@carc.uc.edu
authors.forename: Theresa
authors.initials: T
authors.lastname: Winhusen
authors.forename: Jessica
authors.initials: J
authors.lastname: Walker
authors.forename: Gregory
authors.initials: G
authors.lastname: Brigham
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewis
authors.forename: Eugene
authors.initials: E
authors.lastname: Somoza
authors.forename: Jeff
authors.initials: J
authors.lastname: Theobald
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000378:metabolism* / Q000523:psychology; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D056344:Executive Function / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008875:Middle Aged; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000187:drug effects*; D057566:Self Report
chemical_list: D008694:Methamphetamine; D003042:Cocaine